scholarly journals Aromatase Inhibitors as Adjuvant Treatment for ER/PgR Positive Stage I Endometrial Carcinoma: A Retrospective Cohort Study

2020 ◽  
Vol 21 (6) ◽  
pp. 2227
Author(s):  
Laura Paleari ◽  
Mariangela Rutigliani ◽  
Giacomo Siri ◽  
Nicoletta Provinciali ◽  
Nicoletta Colombo ◽  
...  

Objective: Although endometrial cancer (EC) is a hormone dependent neoplasm, there are no recommendations for the determination of steroid hormone receptors in the tumor tissue and no hormone therapy has ever been assessed in the adjuvant setting. The purpose of this study was to explore the effect of adjuvant aromatase inhibitors (AIs) on progression-free survival (PFS) and overall survival (OS) in patients with early stage and steroid receptors-positive EC. Methods: We retrospectively analyzed clinical and pathological factors in 73 patients with high-risk (49.3%) or low-risk (50.7%) stage I (n = 71) or II (n = 2) endometrial cancer who received by their preference after counseling either no treatment (reference group) or AI. Prognostic factors were well balanced between groups. Expression of estrogen receptor (ER), progesterone receptor (PgR), and Ki-67 index was correlated with clinical outcomes. Results: Univariate and multivariate Cox proportional regression analyses, adjusted for age, grade, stage, depth of myometrial invasion, lymphovascular space invasion, BMI, ER, PgR and Ki-67 labeling index levels, showed that PFS and OS had a trend to be longer in patients receiving AI than in the reference group HR= 0.23 (95% CI; 0.04–1.27) for PFS and HR= 0.11 (95% CI; 0.01–1.36) for OS. Conclusion: Compared with no treatment, AI exhibited a trend toward a benefit on PFS and OS in patients with early stage hormone receptor-positive EC. Given the exploratory nature of our study, randomized clinical trials for ER/PgR positive EC patients are warranted to assess the clinical benefit of AI and the potential predictive role of steroid receptors and Ki-67.

2015 ◽  
Vol 25 (1) ◽  
pp. 75-80 ◽  
Author(s):  
Louis J.M. van der Putten ◽  
Yvette P. Geels ◽  
Nicole P.M. Ezendam ◽  
Hans W.H.M. van der Putten ◽  
Marc P.M.L. Snijders ◽  
...  

ObjectivesTreatment of clinical early-stage endometrioid endometrial cancer (EEC) in The Netherlands consists of primary hysterectomy and bilateral salpingo-oophorectomy. Adjuvant radiotherapy is given when 2 or more the following risk factors are present: 60 years or older, grade 3 histology, and 50% or more myometrial invasion. Lymphovascular space invasion (LVSI) is a predictor of poor prognosis and early distant spread. It is unclear whether adjuvant radiotherapy is sufficient in patients with LVSI-positive EEC.Methods/MaterialsEighty-one patients treated from 1999 until 2011 for stage I LVSI-positive EEC in 11 Dutch hospitals were included. The outcomes of patients with 0 to 1 risk factors were compared with those with 2 to 3 risk factors, and both were compared with the known literature.ResultsEighteen patients presented with recurrent disease, and 12 of those recurrences had a distant component. Overall and distant recurrence rates were 19.2% and 11.5% in patients with 0 to 1 risk factors followed by observation and 25.5% and 17% in patients with 2 to 3 risk factors who received adjuvant radiotherapy. Only 1 patient with grade 1 disease had a recurrence.ConclusionsIn stage I LVSI-positive EEC with 0 to 1 risk factors, observation might not be adequate. Moreover, despite adjuvant radiotherapy, a high overall and distant recurrence rate was observed in patients with 2 to 3 risk factors. The use of systemic treatment in these patients, with the exception of patients with grade 1 disease, should be investigated.


2021 ◽  
pp. 20210151
Author(s):  
Taein An ◽  
Chan Kyo Kim

Objectives: Accurate pre-operative prediction of risk stratification using a non-invasive imaging tool is clinically important for planning optimal treatment strategies, particularly in early-stage endometrial cancer (EC). This study aimed to investigate the utility of apparent diffusion coefficient (ADC) histogram analysis in evaluating the pathological characteristics and risk stratification in patients with Stage I EC. Methods: Between October 2009 and December 2014, a total of 108 patients with surgically proven Stage I EC (endometrioid type = 91; non-endometrioid type = 17) excluding stage ≥II that underwent preoperative 3T-diffusion-weighted imaging without administration of contrast medium were enrolled in this retrospective study. Risk stratification was divided into four risk categories based on the ESMO-ESGO-ESTRO Guidelines: low, intermediate, high-intermediate, and high risk. The ADC histogram parameters (minimum, mean [ADCmean], 10th–90th percentile, and maximum [ADCmax]) of the tumor were generated using an in-house software. The ADC histogram parameters were compared between patients with endometrioid type and non-endometrioid type, between Stage IA and IB, between histological grades, and evaluated for differentiating non-high risk group from high risk group. Inter-reader agreement for tumor ADC measurements was also evaluated. Statistical analyses were performed using the Student’s t-test, Mann–Whitney U test, receiver operating characteristics (ROC) analysis, or intraclass correlation coefficient (ICC). Results: In differentiating endometrioid type from non-endometrioid type EC, all ADC histogram parameters were statistically significant (p < 0.05). In differentiating histological grades, 90th percentile ADC and ADCmax showed significantly higher values in tumor Grade III than in tumor Grade I-II (p < 0.05). In differentiating superficial myometrial invasion from deep myometrial invasion, all ADC histogram parameters were statistically significant (p < 0.05), except ADCmax. In differentiating non-high risk group from high risk group, ADCmean, 75th–90th percentile ADC, and ADCmax were statistically significant (p < 0.05). For predicting the high risk group, the area under the ROC curve of ADCmax was 0.628 and the highest among other histogram parameters. All histogram parameters revealed moderate to good inter-reader reliability (ICC = 0.581‒0.769). Conclusion: The ADC histogram analysis as reproducible tool may be useful for evaluating the pathological characteristics and risk stratification in patients with early-stage EC. Advances in knowledge: ADC histogram analysis may be useful for evaluating risk stratification in early-stage endometrial cancer patients.


2021 ◽  
pp. ijgc-2020-002217
Author(s):  
Elizabeth B Jeans ◽  
William G Breen ◽  
Trey C Mullikin ◽  
Brittany A Looker ◽  
Andrea Mariani ◽  
...  

ObjectivesOptimal adjuvant treatment for early-stage clear cell and serous endometrial cancer remains unclear. We report outcomes for women with surgically staged International Federation of Gynecology and Obstetrics (FIGO) stage I clear cell, serous, and mixed endometrial cancers following adjuvant vaginal cuff brachytherapy with or without chemotherapy.MethodsFrom April 1998 to January 2020, women with FIGO stage IA–IB clear cell, serous, and mixed endometrial cancer underwent surgery and adjuvant vaginal cuff brachytherapy. Seventy-six patients received chemotherapy. High-dose rate vaginal cuff brachytherapy was planned to a total dose of 21 gray in three fractions using a multichannel vaginal cylinder. The primary objective was to determine the effectiveness of adjuvant vaginal cuff brachytherapy and to identify surgicopathological risk factors that could portend towards worse oncological outcomes.ResultsA total of 182 patients were included in the analysis. Median follow-up was 5.3 years (2.3–12.2). Ten-year survival was 73.3%. Five-year cumulative incidence (CI) of vaginal, pelvic, and para-aortic relapse was 1.4%, 2.1%, and 0.9%, respectively. Five-year locoregional failure, any recurrence, peritoneal relapse, and other distant recurrence was 4.4%, 11.6%, 5.3%, and 6.7%, respectively. On univariate analysis, locoregional failure was worse for larger tumors (per 1 cm) (HR 1.9, 95% CI 1.2 to 3.0, p≤0.01). Any recurrence was worse for tumors of at least 3.5 cm (HR 3.8, 95% CI 1.3 to 11.7, p=0.02) and patients with positive/suspicious cytology (HR 4.4, 95% CI 1.5 to 12.4, p≤0.01). Ten-year survival for tumors of at least 3.5 cm was 56.9% versus 86.6% for those with smaller tumors (HR 2.9, 95% CI 1.4 to 5.8, p≤0.01). Ten-year survival for positive/suspicious cytology was 50.9% versus 77.4% (HR 2.2, 95% CI 0.9 to 5.4, p=0.09). Multivariate modeling demonstrated worse locoregional failure, any recurrence, and survival with larger tumors, as well as any recurrence with positive/suspicious cytology. Subgroup analysis demonstrated improved outcomes with the use of adjuvant chemotherapy in patients with large tumors or positive/suspicious cytology.ConclusionAdjuvant vaginal cuff brachytherapy alone without chemotherapy is an appropriate treatment for women with negative peritoneal cytology and small, early-stage clear cell, serous, and mixed endometrial cancer. Larger tumors or positive/suspicious cytology are at increased risk for relapse and worse survival, and should be considered for additional upfront adjuvant treatments, such as platinum-based chemotherapy.


2016 ◽  
Author(s):  
Rohit Raghunath Ranade

Introduction: The role of systematic lymphadenectomy in clinically early stage endometrial cancer is controversial. A number of factors can predict lymph node metastasis including myometrial invasion, tumor grade in endometrial cancers. The purpose of the present study is to evaluate the accuracy of preoperative MRI and intraoperative frozen section in determining the depth of myometrial invasion, cervical involvement, tumor size and lymph nodal status. We also studied the accuracy of preoperative endometrial biopsy and intraoperative frozen section in determining the grade of the tumor. Materials and Methods: Medical records of 235 consecutive cases of clinically early stage endometrial cancer were reviewed retrospectively. A record of depth of myometrial invasion, tumor size, cervical involvement and presence of enlarged lymph nodes was made on a preoperative MRI. Similarly depth of myometrial invasion, tumor size, cervical involvement and grade of the tumor were recorded on an intraoperative frozen section. The grade of the tumor was also recorded on a preoperative endometrial biopsy. Standard statistical calculations were used. Results: The sensitivity and specificity of MRI for myometrial invasion for the first 160 cases were 81.3 and 75%, respectively while that for frozen section were 80 and 96.2%, respectively. For tumor grade the sensitivity and specificity of preoperative endometrial biopsy were 60 and 95.6%, respectively while that of frozen section were 53.8 and 97.6%, respectively. For cervical involvement the sensitivity of MRI and frozen section was 62.5 and 98.4%, respectively. Updated results of the entire cohort of 235 cases will be presented at the conference if selected. Conclusion: Although the sensitivity of both frozen section and MRI for predicting deep myometrial invasion was similar (80 vs 81.3%) but the specificity (96.2 vs 75%) and negative predictive value (92.7 vs 88.2%) of frozen section were superior to MRI. Both preoperative biopsy and intraoperative frozen section had low sensitivity (60 vs 53.8%) for detecting a high grade lesion.


2013 ◽  
Vol 23 (9) ◽  
pp. 1620-1628 ◽  
Author(s):  
Joyce N. Barlin ◽  
Robert A. Soslow ◽  
Megan Lutz ◽  
Qin C. Zhou ◽  
Caryn M. St. Clair ◽  
...  

ObjectiveWe propose a new staging system for stage I endometrial cancer and compare its performance to the 1988 and 2009 International Federation of Gynecology and Obstetrics (FIGO) systems.MethodsWe analyzed patients with 1988 FIGO stage I endometrial cancer from January 1993 to August 2011. Low-grade carcinoma consisted of endometrioid grade 1 to grade 2 lesions. High-grade carcinoma consisted of endometrioid grade 3 or nonendometrioid carcinomas (serous, clear cell, and carcinosarcoma). The proposed system is as follows:IA. Low-grade carcinoma with less than half myometrial invasionIA1: Negative nodesIA2: No nodes removedIB. High-grade carcinoma with no myometrial invasionIB1: Negative nodesIB2: No nodes removedIC. Low-grade carcinoma with half or greater myometrial invasionIC1: Negative nodesIC2: No nodes removedID. High-grade carcinoma with any myometrial invasionID1: Negative nodesID2: No nodes removedResultsData from 1843 patients were analyzed. When patients were restaged with our proposed system, the 5-year overall survival significantly differed (P < 0.001): IA1, 96.7%; IA2, 92.2%; IB1, 92.2%; IB2, 76.4%; IC1, 83.9%; IC2, 78.6%; ID1, 81.1%; and ID2, 68.8%. The bootstrap-corrected concordance probability estimate for the proposed system was 0.627 (95% confidence interval, 0.590–0.664) and was superior to the concordance probability estimate of 0.530 (95% confidence interval, 0.516–0.544) for the 2009 FIGO system.ConclusionsBy incorporating histological subtype, grade, myometrial invasion, and whether lymph nodes were removed, our proposed system for stage I endometrial cancer has a superior predictive ability over the 2009 FIGO staging system and provides a novel binary grading system (low-grade including endometrioid grade 1–2 lesions; high-grade carcinoma consisting of endometrioid grade 3 carcinomas and nonendometrioid carcinomas).


2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e17567-e17567
Author(s):  
Su Yun Chung ◽  
Janice Shen ◽  
Nina Kohn ◽  
Jennifer Hernandez ◽  
Marina Frimer ◽  
...  

e17567 Background: Early-stage endometrial cancer (EEC) with FIGO stage I-II generally has a favorable prognosis and overall survival (OS). However, up to 10% of EEC patients (pts) relapse and risk factors for recurrence remain unclear. We evaluated clinical and histopathologic characteristics of EEC and correlated them with OS and recurrence free survival (RFS) through a single-center retrospective analysis. Methods: We conducted a retrospective chart review on 511 pts with EEC identified by our cancer registry from 1/1/2009 to 12/31/2019. The two main histologic groups were endometrioid adenocarcinomas (E) and other subtypes (O) including carcinosarcoma, undifferentiated, and clear cell carcinomas. Papillary serous histology was excluded. Histopathologic and clinical findings recorded included age, FIGO stage and grade, tumor size, presence of recurrence, adjuvant therapies received, percent of myometrial invasion (MI), and lymphovascular invasion (LVI). OS and RFS were estimated, and each predictor was compared using the log-rank test. The association between OS and each continuous characteristic was examined using the Cox proportional hazards model. Factors significantly associated with OS and RFS in the univariable analysis (p < 0.05) were included in a multivariable analysis to examine the joint effects of those factors on survival. Results: A total of 511 cases were reviewed. The analysis included 501 pts (E = 485, O = 16), of which 47 had recurrent disease (E = 45, O = 2) and 17 had died without recurring (E = 15, O = 2) as of their last follow-up. Overall median age was 63 years. Factors significantly associated with recurrence in the multivariable analysis were FIGO grade, (Hazard Ratios (HR): Grade 2 vs 1: 1.95, 95% CI: 1.06-3.58, p = 0.0320, Grade 3 vs 1: 2.88, 95% CI: 1.50-5.52, p = 0.0015), LVI (HR: 2.03, 95% CI: 1.10-3.75, p = 0.0244), and greater than 50% of MI (HR: 3.15, 95% CI: 1.35-7.36, p = 0.0080). The overall RFS was 92% and 86% at three and five years, respectively. On univariate analysis, among pts with a measurable tumor size (n = 446), larger tumors were not significantly associated with OS (p = 0.65) but was associated with increased recurrence (HR 1.22, 95% CI: 1.10-1.37, for a unit increase, p = 0.0003). On univariate analysis, pts who received adjuvant therapy were more likely to recur (p = 0.0002) with RFS of 86% and 76% at three and five years respectively, versus RFS of 94% and 90%, for those who did not. Conclusions: We confirmed the clinical and histopathologic characteristics that are currently considered to increase risk of recurrence in EEC. On multivariate analysis, risk of recurrence was associated with FIGO grades 2 and 3, presence of LVI, and > 50% MI. A limitation of this study is the lack of molecular analysis. Further molecular stratification may help us identify the subset of pts who are at high risk of recurrence, enabling customized adjuvant therapy in EEC.


Author(s):  
John M. Anderson ◽  
Tam Nguyen ◽  
Joel Childers ◽  
Alton V. Hallum ◽  
Earl Surwitt ◽  
...  

2004 ◽  
Vol 14 (4) ◽  
pp. 665-672 ◽  
Author(s):  
F. Alexander-Sefre ◽  
N. Singh ◽  
A. Ayhan ◽  
J. M. Thomas ◽  
I. J. Jacobs

BackgroundThere is a strong correlation between disease mortality and the depth of myometrial invasion in stage I endometrial cancer (EC). Current assessment of the depth of invasion relies on light microscopy. Tumor cells can evade detection by light microscopy if they are vastly outnumbered by myometrial cells. Immunohistochemical (IHC) techniques against pancytokeratins (PCKs) have a great potential in the detection of such isolated cells.ObjectivesTo investigate the application of IHC techniques in the identification of isolated infiltrating tumor cells within myometrium and assess its significance in clinically stage I EC.MethodsA single representative tissue block containing the deepest myometrial invasion by the tumor was selected for 90 patients with stage I EC. Sections from each block were immunostained in accordance with established streptavidin–biotin peroxidase method using a mouse monoclonal antikeratin clone AE1/AE3. Myometrium was re-examined to identify deeper myometrial invasion that had escaped detection on hematoxylin and eosin (H&E) section. The clinical records were reviewed, and following data were collected: age, race, parity, presentation, associated medical disorders (obesity, diabetes, and hypertension), use of tamoxifen or hormone replacement therapy, menopausal state, recurrence, and survival.ResultsOf 90 cases, deeper myometrial invasion was detected on IHC sections in seven cases (7.7%). In five of these seven cases, isolated tumor cells surrounded by inflammatory cells were noted 0.2–1.2 mm deeper within the myometrium than that detected by H&E staining. In the remaining two cases, the deeper extension seen was the result of examining serial levels through the tumor block; in these cases, deeper infiltration should have been apparent on H&E sections. Follow-up data was available in 72 of the 90 cases. A trend was noted between the presence of isolated tumor cells deeper within myometrium on IHC and tumor recurrence (P = 0.056). The 2-year recurrence-free survival was 40% for the group with IHC evidence of deeper invasion compared with 89% for the group without (P = 0.005). Similarly, analysis of cause-specific and overall survival revealed significant differences between the two groups (P = 0.038 and P = 0.026, respectively).ConclusionsIn this study, we have shown that it is possible to identify deeper level of myometrial invasion by tumor cells using an IHC technique. IHC-detected deeper invasion is an uncommon event and may be a feature of more aggressive tumors with greater potential for recurrence and lower survival.


2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 5036-5036 ◽  
Author(s):  
R. G. Moore ◽  
A. K. Brown ◽  
C. M. Miller ◽  
D. Badgwell ◽  
Z. Lu ◽  
...  

5036 Background: Approximately 40,880 new cases of uterine cancer are diagnosed in the U.S. annually resulting in 7,310 deaths. Uterine cancer is surgically staged and 75% of patients present with stage I disease. Patients with stage I tumors with intermediate to high risk factors have a recurrence rate of 20 to 30%. Serum CA125 is elevated in 75% of patients with advanced stage disease and in only 17% of patients with early stage disease. The use of CA125 for the detection of recurrent disease is limited at best. Only 25% of patients with asymptomatic recurrent disease have an elevated CA125. A better marker indicating early recurrent disease is needed. The objective of this study was to examine the value of a novel serum tumor marker HE4 in endometrial cancer. Methods: Serum samples from two prospective IRB approved studies at two institutions were analyzed to compare HE4 with CA125 in patients who had surgical staging for uterine cancer. Normal controls were obtained from healthy patients. Informed consent was obtained from all patients and blood samples were drawn pre-operatively. HE4 and CA125 levels were determined using assays from Fujirebio Diagnostic Inc. ROC curves were constructed for each tumor marker and the sensitivity at a set specificity of 95% was determined. Results: Serum from 156 controls and 233 patients with surgically staged endometrial cancer; (151 stage I, 21 stage II, 47 stage III and 14 stage IV) were examined. The area under the ROC curves (ROC-AUC) for HE4 and CA125 were determined and compared ( Table1 ). At 95% specificity, the sensitivity for differentiation of controls versus all stages was 44.9% for HE4 compared to 25.2% for CA125 (p = 0.0001). For stage I cases, HE4 showed an improvement in the sensitivity of 20.5% compared to CA125 (37.1% vs 16.6%, p = 0.0001). Conclusions: HE4 is elevated in all stages of endometrial cancer and has a greater sensitivity for discrimination from normal controls compared to CA125. As well, HE4 is elevated in early stage endometrial cancer and should be investigated as a marker for early recurrent disease. [Table: see text] [Table: see text]


2021 ◽  
Vol 11 ◽  
Author(s):  
Bi Cong Yan ◽  
Xiao Liang Ma ◽  
Ying Li ◽  
Shao Feng Duan ◽  
Guo Fu Zhang ◽  
...  

BackgroundOvarian preservation treatment (OPT) was recommended in young women with early-stage endometrial cancer [superficial myometrial invasion (MI) and grades (G) 1/2-endometrioid adenocarcinoma (EEC)]. A radiomics nomogram was developed to assist radiologists in assessing the depth of MI and in selecting eligible patients for OPT.MethodsFrom February 2014 to May 2021, 209 G 1/2-EEC patients younger than 45 years (mean 39 ± 4.3 years) were included. Of them, 104 retrospective patients were enrolled in the primary group, and 105 prospective patients were enrolled in the validation group. The radiomics features were extracted based on multi-parametric magnetic resonance imaging, and the least absolute shrinkage and selection operator algorithm was applied to reduce the dimensionality of the data and select the radiomics features that correlated with the depth of MI in G 1/2-EEC patients. A radiomics nomogram for evaluating the depth of MI was developed by combing the selected radiomics features with the cancer antigen 125 and tumor size. Receiver operating characteristic (ROC) curves were used to evaluate the diagnostic performance of the radiomics nomogram and of radiologists without and with the aid of the radiomics nomogram. The net reclassification index (NRI) and total integrated discrimination index (IDI) based on the total included patients to assess the clinical benefit of radiologists with the radiomics nomogram were calculated.ResultsIn the primary group, for evaluating the depth of MI, the AUCs were 0.96 for the radiomics nomogram; 0.80 and 0.86 for radiologists 1 and 2 without the aid of the nomogram, respectively; and 0.98 and 0.98 for radiologists 1 and 2 with the aid of the nomogram, respectively. In the validation group, the AUCs were 0.88 for the radiomics nomogram; 0.82 and 0.83 for radiologists 1 and 2 without the aid of the nomogram, respectively; and 0.94 and 0.94 for radiologists 1 and 2 with the aid of the nomogram, respectively. The yielded NRI and IDI values were 0.29 and 0.43 for radiologist 1 and 0.23 and 0.37 for radiologist 2, respectively.ConclusionsThe radiomics nomogram outperformed radiologists and could help radiologists in assessing the depth of MI and selecting eligible OPTs in G 1/2-EEC patients.


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